The immunoglobulin (Ig) gene superfamily comprises a large number of cell surface glycoproteins that share sequence homology with the V and C domains of antibody heavy and light chains. These molecules function as receptors for antigens, immunoglobulins and cytokines as well as adhesion molecules, and play important roles in regulating the complex cell interactions that occur within the immune system (A. F. Williams et al., Annu. Rev. Immuno. 6:381-405, 1988, T. Hunkapiller et al., Adv. Immunol. 44:1-63, 1989).
Several human immunodeficiency diseases derive from gene defects or from functional deregulation of the Ig superfamily proteins. Examples are Hyper-IgM Immunodeficiency (HIM) caused by a defect in the gene encoding the ligand for CD40 (R. C. Allen et al., Science 259:990-993, 1993), X-linked Severe Combined Immunodeficiency (XSCID) caused by mutations of the IL-2 receptor (M. Noguchi et al., Cell 73:147-157, 1993) and IgA deficiency (IgA-D) linked to HLA-DQb (M. A. French et al., Immunol. Today 11:271-274, 1990).
This indicates that these receptors have an established, proven history as therapeutic targets. Clearly there is a need for identification and characterization of rather receptors which can play a role in preventing, ameliorating or correcting dysfunctions or diseases, including, but not limited to, Hyper-IgM Immunodeficiency (HIM), X-linked Severe Combined Immunodeficiency (XSCID), and IgA deficiency (IgA-D).